Although several cervical cancer screening programs and demonstrations have taken place in southern Africa, only limited evaluations in the real-world setting have assessed program effectiveness, cost, and barriers/facilitators. Furthermore, even though numerous projects have been initiated, only a few successful programs are in operation today. Lessons learned from successful programs have not been synthesized and disseminated to foster scale-up of cost-effective implementation strategies. Given the substantial prevalence of human immunodeficiency virus (HIV) in southern Africa, which significantly increases the risk for cervical cancer, there is an urgent need to scale up preventio and screening services. The specific aims of the proposed research to address the gaps in the evidence base are as follows: Aim 1: Perform systematic process evaluation of the successful Cervical Cancer Prevention Program in Zambia (CCPPZ) to identify lessons for scaling up services in other sub-Saharan countries. Aim 2: Undertake comprehensive assessment of stakeholder perspectives on current program operations to identify barriers and facilitators and innovative financing arrangements to ensure sustainability. Aim 3: Develop a novel microsimulation model to assess cost and effectiveness of interventions and strategies for scaling up cervical cancer prevention and screening at the population level under real-world conditions that include budget and capacity constraints. Successful implementation of the project aims will provide evidence-based implementation guidelines on the optimal selection of prevention and screening interventions to reduce incidence of and mortality from cervical cancer. We will model the impact of behavior change (for example, sexual behavior affects rate of HIV and human papillomavirus [HPV] infections), prevention with HPV vaccination, and screening with visual inspection techniques and the new rapid HPV test; all scenarios will be evaluated under a variety of budget and capacity constraints. This comprehensive approach will allow policymakers to view the changes in cost and outcomes when interventions focusing on both HIV and cervical cancer are implemented rather than when a single-disease-focused approach is used. The process evaluation of CCPPZ and stakeholder assessment will provide best practices, key lessons, review of innovative financing options, and synthesis of barriers and facilitators to guide large-scale program implementation. To ensure generalizability of the findings to other sub-Saharan African nations, we will actively engage health professionals from African countries, and the findings will be disseminated and debated in two symposiums specifically convened for this purpose.